Rational Stabilization of Helix 2 of the Prion Protein Prevents Its Misfolding and Oligomerization

Designed stabilization of helix 2 of the mouse prion protein is shown to lead to an increase in global stability of the protein. Studies of hydrogen exchange coupled to mass spectrometry confirm that the increase in stability is confined primarily to helix 2, and that it accounts for the global stabilization of the protein. Importantly, such localized stabilization of the protein can completely inhibit its ability to form oligomers and slows down amyloid fibril formation.